Rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ, reduces pulmonary inflammatory response in a rat model of endotoxemia

Objective: The effect of rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, on pulmonary inflammation in endotoxemia was investigated. Materials and methods: Male Wistar rats were given either lipopolysaccharide (LPS, 6 mg/kg i.v.) or saline, pretreated with rosiglitazone (0.3 mg/kg i.v.) or its vehicle (dimethyl sulphoxide) 30 min before LPS. The selective PPAR-γ antagonist GW9662 (0.3 mg/kg i.v.) was given 20 min before rosiglitazone. Wet/dry weight (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA) as well as TNF-α and CINC-1 concentrations were measured in lung tissues 4 h after LPS injection. Expression of ICAM-1, NF-κB p65 and PPAR-γ were also determined by immunohistochemistry or Western blot analysis. Results: Rosiglitazone pretreatment significantly attenuated the increases in W/D ratio, MPO activity and MDA levels, and reduced pulmonary overproduction of TNF-α and CINC-1 as well as expression of ICAM-1 following endotoxemia. Rosiglitazone also inhibited the nuclear localization of NF-κB and up-regulated the expression of PPAR-γ protein. The specific PPAR-γ antagonist GW9662 abolished the effect of rosiglitazone. Conclusion: These findings suggest that PPAR-γ agonists might be used as therapeutic agents in the therapy of inflammatory lung injury related to endotoxemia. Received 8 January 2005; returned for revision 6 July 2005; returned for final revision 20 July 2005; accepted by M. Katori 31 July 2005     

Differentiation of endometrial stromal cells in vitro: down-regulation of suppression of the cell cycle inhibitor p57 by HOXA10?

Decidualization is a critical step during embryo implantation that is characterized by the differentiation of endometrial stromal cells (ESC) into decidua cells. However, the mechanism of differentiation remains largely unknown. Previously, it has been shown that the null function of homeo box A10 (HOXA10) causes defects in both implantation and decidualization, suggesting that the HOXA10 signalling pathway is likely to be involved in uterine decidualization. In the present study, we determined the expression and subcellular distribution of HOXA10 and its downstream molecule, p57, in ESC during in vitro decidualization induced by a combination of 8-bromo-cAMP and medroxyprogesterone acetate. We demonstrated that the HOXA10 was down-regulated while in contrast, p57 was up-regulated in the process of decidualization. Immunocytochemistry and transient expression of the HOXA10 tagged with green fluorescence protein revealed that there were no differences in the HOXA10 subcellular localization between the induced and non-induced ESC. Our results suggest that the down-regulation of HOXA10 may contribute to increased p57 and that up-regulation of p57 likely plays an important role in ESC differentiation in the process of decidualization. The progesterone receptor pathway may participate in promoting ESC to exit the cell cycle and enter differentiation.     

急性肺血栓栓塞症兔TNF-α、IL-8、IL-10水平及地塞米松的影响

目的:探讨兔急性肺血栓栓塞症(PTE)时血浆及支气管肺泡灌洗液(BALF)中TNF-α,IL-8、IL-10的水平和地塞米松(Dex)的影响。方法:采用自体血栓回输法建立兔急性PTF模型。36只兔随机分为对照组、Dex治疗组和PTE模型组。用ELISA方法检测上述细胞因子(CK)水平,术毕肺组织行病理观察。结果:栓塞后上述CK均有升高,治疗后TNF-α、IL-8均有下降,IL-10变化不明显。组织病理学可见栓塞后肺动脉内血栓形成,肺组织萎缩、出血、炎性反应明显,Dex治疗后肺组织病理改变明显减轻。结论:PTE后促炎性CK在引起肺部炎性反应和肺组织及肺动脉病损中起了重要作用,抗炎治疗可以明显减轻CK引起的这种损伤。抗炎治疗能降低PTE急性期病死率,改善远期预后,CK可能起了很重要的作用。     

磷脂酰肌醇3激酶对TNF-α诱导的大鼠气道平滑肌细胞增殖、凋亡和转化生长因子β1表达的影响

目的 探讨磷脂酰肌醇3激酶（PI3-K）对TNF-α诱导的大鼠气道平滑肌细胞（ASMC）增殖、凋亡和转化生长因子β1（TGF-β1）表达的影响.方法 以肿瘤坏死因子-α（TNF-α）及PI3-K特异性抑制剂wortmannin作为工具药,分别将TNF-α、TNF-α＋wortmannin接种ASMC,置37℃,5%CO2培养箱中培养.逆转录聚合酶链式反应（RT-PCR）检测PI3-Kp85α、TGF-β1 mRNA表达,免疫细胞化学染色法检测PI3-Kp85α、PCNA、Bcl-2蛋白表达及定位,Sandwich ELISA检测NF-κB活性,四甲基偶氮唑蓝（MTT）微量比色法测定ASMC增殖,AnnexinV/PI双标记流式细胞仪分析法检测细胞凋亡,ELISA测定TGF-β1蛋白质含量.结果 （1）培养的ASMC PI3-K p85α的阳性定位在胞浆.TNF-α组ASMC PI3-Kp85α mRNA及蛋白表达水平均显著高于对照组及TNF-α＋wortmannin组（P＜0.01）;（2）TNF-α组ASMCNF-κB活性与对照组相比显著增高（P＜0.01）,TNF-α＋wortmannin组NF-κB活性与TNF-α组相比显著降低（P＜0.01）;（3）TNF-α组ASMC的增殖反应与对照组及TNF-α＋wortmannin组相比显著增加（P＜0.01）;TNF-α组细胞凋亡率与对照组相比差异无统计学意义（P＞0.05）,TNF-α＋wortmannin组细胞凋亡率显著高于TNF-α组及对照组（P＜0.01）.（4）TNF-α组ASMC的PCNA、Bcl-2蛋白表达量均显著高于对照组及TNF-α＋wortmannin组（P＜0.01）;（5）TNF-α组ASMC的TGF-β1的mRNA表达水平、培养液上清TGF-β1的蛋白质含量均显著高于对照组及TNF-α＋wortmannin组（P＜0.01）.结论 PI3-K可能参与调控TNF-α诱导的大鼠气道平滑肌细胞的增殖、凋亡及TGF-β1的表达和分泌,NF-κB作为PI3-K的下游信号参与此过程.     

川芎嗪对人外周血淋巴细胞蛋白激酶C通道的影响

目的:探讨川芎嗪(LTZ)对正常人外周血淋巴细胞(PBL)蛋白激酶C(PKC)通道在受到与哮喘有关的炎症介质刺激时所发生的功能变化是否有影响。方法:取63例健康人外周静脉血各10mL,分离PBL,分4批分别给予以下处理后,采用-ATP催化活性测定法检测细胞胞膜、胞浆及总PKC活性。(1)分3组即5g/LLTZ处理组(6例)、5μmol/LPKC阻断剂Ro31-8220处理组(6例)和对照组(6例,以下各批均以此组为阴性对照组);(2)共3组分别用100nmol/L乙酰甲胆碱(Mch,5例)、5g/LLTZ+100nmol/LMch(5例)或5μmol/LRo31-8220+100nmol/LMch(5例)处理。(3)共3组分别采用100nmol/L组胺、5g/LLTZ+100nmol/L组胺(5例)或5μmol/LRo31-8220+100nmol/L组胺(5例)处理。(4)共3组分别用100nmol/LPMA(5例)、5g/LLTZ+100nmol/LPMA(5例)或5μmol/LRo31-8220+100nmol/LPMA(5例)。结果(1)LTZ对正常人PBL胞膜、胞浆及总PKC活性均无明显影响;(2)乙酰甲胆碱及组胺均可促进正常人PBL胞膜PKC活性增加,LTZ对该作用有抑制效应(P<0.05)。(3)LTZ对PMA诱发正常人PBL胞膜PKC活性增加的效应有抑制作用(P<0.05)。结论:川芎嗪对正常人PBLPKC通道在受到与哮喘有关的炎症介质刺激时所发生的活化有一定的抑制作用,该作用可能是川芎嗪对哮喘疾病具有防治意义的机制之一。     

针刺对多囊卵巢综合征大鼠卵巢TGF-α、EGFR表达的影响

目的:研究针刺对多囊卵巢综合征(PCOS)大鼠卵巢转化生长因子α(TGF-α)、表皮生长因子受体(EGFR)表达的影响,探讨针刺促排卵的作用机制。方法:24日龄雌性大鼠颈背部皮下注射脱氢表雄酮(DHEA)的油溶液制作(PCOS)模型,对照组同期皮下注射油剂。PCOS大鼠随机分为模型组和针刺组。模型组不作处理,针刺组大鼠从80日龄起针刺关元、中极、双侧三阴交、双侧子宫穴,1次/天,15min/次,连续6周。治疗结束后各组大鼠断头处死,迅速取血并分离血清,-20℃冰箱保存,待测性激素水平。摘取双侧卵巢,称重,4%多聚甲醛固定,作HE染色和免疫组织化学染色。结果:与模型组相比,针刺组卵巢湿重、卵巢TGF-α、EGFR表达及血清睾酮(T)、雌二醇(E2)水平均显著降低(P<0.01),而卵泡刺激素(FSH)、黄体生成素(LH)、孕酮(P4)水平差异无统计学意义(P>0.05)。结论:针刺能显著降低PCOS大鼠卵巢TGF-α及EGFR的表达,抑制TGF-α对卵巢和激素合成的作用,改善PCOS大鼠多囊样变和高雄激素血症,促进排卵。     

Combination of Quantitative Computed Tomography and Blood Biochemistry for Evaluating the Relationship Between Nutrition and Bone Mineral Density in Patients on Maintenance Hemodialysis

PurposeTo investigate the effect of nutritional factors on bone mineral density (BMD) using quantitative computed tomography combined with blood biochemistry in patients on maintenance hemodialysis (MHD).MethodsSixty patients on MHD were divided into osteopenia (n = 20) and nonosteopenia (n = 40) groups. BMD, fat, and muscle mass were measured by quantitative computed tomography. The calcification of coronary artery and hilar lymph node and computed tomography attenuation values of the liver and spleen were also analyzed. Differences between the two groups were compared, and the risk factors for osteopenia were analyzed by logistic regression analysis.ResultsPatients in the osteopenia group had lower albumin levels than those in the nonosteopenia group (37.84 ± 3.00 vs 42.03 ± 4.05 g/L; P < .001). Logistic regression showed that patients with lower albumin levels had a higher risk of osteopenia (odds ratio, 1.462; 95% confidence interval, 1.313–1.801; P = .003). BMD was negatively correlated with fat mass (r = ?0.365, P = .004) and positively correlated with the ratio of muscle mass to fat mass (r = 0.431, P = .001). There was no significant difference in the rate of calcification of coronary artery or hilar lymph nodes between the two groups. Computed tomography values of the liver and spleen were positively correlated with the duration of dialysis (r = 0.55, P = .001; r = 0.42, P < .001, respectively).ConclusionLow albumin levels are associated with an increased risk of osteopenia in patients on MHD. Abdominal fat is a risk factor for reduction in BMD in MHD patients, and the ratio of abdominal muscle mass to fat mass is a protective factor for BMD.     

国产重组人促卵泡激素在辅助生殖技术控制性超促排卵的临床应用

目的评价国产重组人促卵泡激素(recombinant human follicle-stimulating hormone,rhFSH)用于辅助生殖技术(assisted reproductive technology,ART)控制性超促排卵(controlled ovarian hyperstimulation,COH)的有效性及安全性。方法本试验采用多中心、随机、双盲、阳性平行对照、非劣效研究方法,于2017年7月至2019年6月间选取6家生殖医学中心纳入卵巢储备正常的不孕女性进行ART的COH治疗。受试者随机分为试验组(国产rhFSH,n=134)和对照组(进口rhFSH,n=133),研究过程中因各种因素排除受试者共8例,试验组7例,对照组1例,最终依照研究方案完成试验的受试者试验组127例,对照组132例。比较两组受试者COH周期中获得的卵母细胞总数、rhFSH用药情况、卵母细胞受精率、优质胚胎数、临床妊娠率、活产率、新生儿情况及不良反应发生率等指标。结果试验组和对照组在COH周期中获得的卵母细胞总数分别为(13.0±5.8)枚和(12.9±5.7)枚,差异无统计学意义(P>0.05);在82例卵胞质内单精子显微注射(intracytoplasmic sperm injection,ICSI)受试者中,试验组(39例)获得MII卵母细胞数[(9.9±3.9)枚]显著高于对照组(43例)[(7.5±3.0)枚,P=0.003];卵母细胞受精率试验组[63.82%(1048/1642)]显著高于对照组[56.19%(958/1705),P<0.001]。rhFSH用药时间和总量、优质胚胎数、临床妊娠率、早产率、活产率、新生儿异常发生率、新生儿体质量、Apgar评分等两组间差异无统计学意义(P均>0.05);治疗期间卵巢过度刺激综合征(ovarian hyperstimulation syndrome,OHSS)和其他不良反应发生率差异无统计学意义(P均>0.05),且均为进口rhFSH已知的不良反应。结论在卵巢储备正常的不孕女性中使用相同卵巢刺激治疗方案,国产rhFSH有效性及安全性与进口rhFSH相当。     

Road Traffic and Urban Form Factors Correlated with the Incidence of Lung Cancer in High-density Areas: An Ecological Study in Downtown Shanghai,China

The incidence of lung cancer is affected by air pollution, especially in high-density urban areas with heavy road traffic and dense urban form. Several studies have examined the direct relationship between lung cancer incidence and road traffic as well as urban form. However, the results are still inconsistent for high-density urban areas. This study focused on urban form and road traffic, aiming at revealing their relationship with lung cancer incidence in high-density urban areas at the neighborhood level. For this, an ecological study was conducted in downtown Shanghai to identify important indicators and explore quantitative associations. Negative binomial regression was fitted with lung cancer incidence as the dependent variable. The independent variables included indicators for road traffic and urban form, greenness, demographic, and socio-economic factors. The results showed that building coverage, averaged block perimeter area ratio, density of metro station without the glass barrier system, and the percentage of low-quality residential land were positively correlated with lung cancer incidence in the neighborhood, while population density was negatively correlated with lung cancer incidence. This study found a strong self-selection effect of socio-economic factors in the relationship between lung cancer incidence and greenness. These results may be useful for conducting health impact assessments and developing spatial planning interventions for respiratory health in high-density urban areas.     

A Qualitative Study: Perceived Barriers and Facilitators to Nutrition Standard Adherence by In-home Childcare Providers

BackgroundThe Child and Adult Care Food Program (CACFP) nutrition standards may present food purchasing, preparation, and feeding challenges for caregivers of young children.ObjectiveTo elucidate perceived barriers and facilitators faced by in-home childcare providers to following the CACFP food and beverage nutrition standards.DesignVirtual, semistructured individual interviews elicited perceptions from a cross section of low-income, in-home childcare providers in Michigan.Participants/settingsTwenty childcare providers of various races, ethnicity, urban and rural residence, and licensure status.AnalysisThematic coding analysis with NVivo (ver12.0) to organize and interpret data.ResultsFour primary barriers to adhering to the CACFP nutrition standards emerged including (1) noncompliant food preferences of children and providers; (2) higher cost and lower availability of CACFP-approved items; (3) celebrations and food rewards; (4) excessive time and effort needed to prepare foods and beverages, especially with dietary restrictions for some children. Ten perceived facilitators included (1) using nutrition education available through community organizations; (2) finding convenient and easy ways to prepare foods and beverages; (3) using CACFP and Special Supplemental Nutrition Program for Women, Infants, and Children guidelines and funding; (4) increasing variety of foods and beverages by using a menu or recalling items recently served; (5) modeling eating healthful foods and encouraging sampling of new foods and beverages; (6) mixing preferred foods/beverages with less preferred; (7) using nutrition information available from social media and from peers; (8) allowing children to choose foods and beverages; (9) serving the same eligible food and beverages to all children; and (10) provider concern about impact of foods and beverages on children’s health and behavior.ConclusionsResults from this study can inform nutrition education from community organizations that occurs in tandem with CACFP sponsor organizations. In addition, they can be utilized to address state-level licensure regulations and quality improvement rating systems that include nutrition standards childcare providers are encouraged or required to follow.